In Salmonella typhimurium the cysteine biosynthetic pathway is controlled by a combination of feedback inhibition of serine transacetylase and a system of positive gene control in which the cysteine precursor O-acetylserine is an internal inducer. We shall attempt to purify the cysB gene product, which is a regulatory protein necessary for the expression of the cysteine biosynthetic pathway, by cloning cysB on a multiple copy-number plasmid which can be used to construct an over-producing strain. In addition, the enzyme O-acetylserine sulfhydrylase-B will be purified and its role in in vivo cysteine biosynthesis will be determined. In studies designed to characterize certain aspects of mammalian sulfur metabolism, the effects of 2'-deoxyadenosine on S-adenosylmethionine and S-adenosylhomocysteine metabolism will be examined in order to determine whether this nucleoside causes a defect in transmethylation in cultured cells or in patients with heritable adenosine deaminase deficiency. Other factors influencing the metabolism of methionine, S-adenosylmethionine, S-adenosylhomocysteine and homocysteine will be sought for and characterized. In addition we plan to elucidate the manner in which cordycepin inhibits RNA methylation in cultured cells.